Once daily Bromelain-based enzymatic debridement of venous leg ulcers versus gel vehicle (placebo) and non-surgical standard of care: a three-arm multicenter, double blinded, randomized controlled study

被引：2

作者：

Shoham, Yaron ^{[1
]}

Snyder, Robert J. ^{[2
]}

Levy, Yael Katz ^{[2
]}

Zarbiv, Keren David ^{[2
]}

Klinger, Ety ^{[2
]}

Kramer, Miri ^{[2
]}

Dove, Cyaandi R. ^{[3
]}

Avrahami, Ram ^{[4
]}

Reyzelman, Alex ^{[5
]}

Sigal, Felix ^{[6
]}

Tovmassian, Gregory ^{[7
]}

Shapira, Eyal ^{[8
]}

Harats, Moti ^{[9
]}

Perez-Clavijo, Francisco ^{[10
]}

Lantis, John C. ^{[11
,12
]}

Cazzell, Shawn M. ^{[13
]}

Dhillon, Yadwinder S. ^{[14
]}

Cuffy, Cherison A. ^{[15
]}

Egozi, Dana ^{[16
,17
]}

Vayser, Dean ^{[18
]}

Singer, Adam J. ^{[19
]}

Galperin, Richard C. ^{[20
]}

Hanft, Jason R. ^{[21
]}

Martinez, Cindy ^{[22
]}

Shalom, Avshalom ^{[23
]}

Toutous-Trellu, Laurence ^{[24
]}

Rosenberg, Lior ^{[1
]}

机构：

[1] Ben Gurion Univ Negev, Soroka Univ, Dept Plast & Reconstruct Surg, Fac Hlth Sci,Med Ctr, Beer Sheva, Israel

[2] MediWound Ltd, Yavne, Israel

[3] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX USA

[4] Rabin Med Ctr, Dept Vasc Surg, Petah Tiqwa, Israel

[5] Samuel Merritt Univ, UCSF Ctr Limb Preservat, Calif Sch Podiatr Med, Dept Med, San Francisco, CA USA

[6] Foot & Ankle Clin, Podiatr Med, Los Angeles, CA USA

[7] Samuel Merritt Univ, Calif Sch Podiatr Med, San Francisco, CA USA

[8] Shamir Med Ctr, Dept Plast Surg, Zerifin, Israel

[9] Sheba Med Ctr, Dept Plast & Reconstruct Surg, Tel Hashomer, Israel

[10] Podiatry Care Partners, Doral, FL USA

[11] Mt Sinai West Hosp, New York, NY USA

[12] Icahn Sch Med, New York, NY USA

[13] LPP Res, Limb Preservat Platform, Fresno, CA USA

[14] AZ Wound Titan Clin Res, Phoenix, AZ USA

[15] Barry Univ, Sch Podiatr Med, Miami Shores, FL USA

[16] Kaplan Med Ctr, Dept Plast & Reconstruct Surg, Rehovot, Israel

[17] Hebrew Univ Jerusalem, Fac Med, Jerusalem, Israel

[18] Scripps Clin Med Grp, Foot & Ankle Ctr, Dept Orthoped, San Diego, CA USA

[19] SUNY Stony Brook, Renaissance Sch Med, Dept Emergency Med, Stony Brook, NY USA

[20] Methodist Dallas Med Ctr, Dallas, TX USA

[21] Doctors Res Network, South Miami, FL USA

[22] Project 4 Res Inc, Miami, FL USA

[23] Meir Med Ctr, Dept Plast Surg, Kefar Sava, Israel

[24] Univ Hosp Geneva, Geneva, Switzerland

来源：

ECLINICALMEDICINE | 2024年 / 75卷

关键词：

VLU; Venous leg ulcer; Enzymatic debridement; EscharEx; RCT; Chronic wounds; CADEXOMER IODINE; CHRONIC WOUNDS; OPEN-LABEL; MANAGEMENT; OUTCOMES; COMPARE; TRIAL; AGENT;

D O I：

10.1016/j.eclinm.2024.102750

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background Debridement is considered the fi rst step in treatment of chronic wounds, however, current enzymatic and autolytic debridement agents are slow or ineffective. Previous studies have shown positive initial results with EscharEx (R) (EX-02 formulation), a Bromelain-based enzymatic debridement agent in development for chronic wounds. The main objective of this study was to assess its efficacy fi cacy in debriding venous leg ulcers (VLU), compared to gel vehicle (GV) as a placebo control and to non-surgical standard of care (NSSOC). Methods A prospective, randomized, multicenter, placebo-controlled trial in patients with VLU from 20 medical centers and clinics in the United States, Switzerland and Israel was undertaken. Patients were treated with daily topical applications of either EX-02, GV, or NSSOC (in a 3:3:2 ratio), until reaching complete debridement or up to 8 daily treatments (within 2 weeks), and then followed-up for up to 14 weeks. The primary efficacy fi cacy endpoint was the incidence of complete debridement. This study is registered with ClinicalTrials.gov (NCT03588130) and EudraCT (number 2020-004861-38). Findings A total of 196 patients were enrolled, and 119 randomized (between November 12th, 2019, and February 15th, 2022); 46 to the EX-02 arm, 43 to the GV arm, and 30 to the NSSOC arm. Eight patients dropped out of the study (2 in EX-02, 2 in GV, 4 in NSSOC). The incidence of complete debridement within 8 daily treatments was 63% (29/46 patients) in the EX-02 arm as compared to 30.2% (13/43 patients) in the GV arm (p = 0.004) and 13.3% (4/30 patients) in the NSSOC arm (p < 0.001). Sixty-five fi ve patients reported wound related adverse events throughout the study; 24 (52.2%), 27 (62.8%) and 14 (46.7%) patients in the EX-02, GV and NSSOC arms (p = NS). No deaths occurred during the study. Interpretation EX-02 lead to a significantly fi cantly higher incidence of complete debridement as compared to GV and NSSOC, without significant fi cant safety issues. Additional studies are needed to explore the benefits fi ts of EX-02 in VLU and other chronic wound etiologies.

引用

页数：14